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Characterization of the conformational fluctuations in the Josephin domain of ataxin-3.

ABSTRACT: As for a variety of other molecular recognition processes, conformational fluctuations play an important role in the cleavage of polyubiquitin chains by the Josephin domain of ataxin-3. The interaction between Josephin and ubiquitin appears to be mediated by the motions of ?-helical hairpin that is unusual among deubiquitinating enzymes. Here, we characterized the conformational fluctuations of the helical hairpin by incorporating NMR measurements as replica-averaged restraints in molecular dynamics simulations, and by validating the results by small-angle x-ray scattering measurements. This approach allowed us to define the extent of the helical hairpin motions and suggest a role of such motions in the recognition of ubiquitin.

SUBMITTER: Sanfelice D

PROVIDER: S-EPMC4269769 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Characterization of the conformational fluctuations in the Josephin domain of ataxin-3.

Sanfelice Domenico D De Simone Alfonso A Cavalli Andrea A Faggiano Serena S Vendruscolo Michele M Pastore Annalisa A

Biophysical journal 20141201 12

As for a variety of other molecular recognition processes, conformational fluctuations play an important role in the cleavage of polyubiquitin chains by the Josephin domain of ataxin-3. The interaction between Josephin and ubiquitin appears to be mediated by the motions of α-helical hairpin that is unusual among deubiquitinating enzymes. Here, we characterized the conformational fluctuations of the helical hairpin by incorporating NMR measurements as replica-averaged restraints in molecular dyna ...[more]

PMID: 25517158

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